文献类型：期刊文献

中文题名：As_2O_3联合AZT通过激活caspase-3通路抑制肝癌HepG2细胞的增殖

英文题名：As_2O_3 in combination with AZT suppresses the proliferation of hepatoma HepG2 cells through activating caspase-3 pathway

作者：刘玉[1];原凌燕[1];楚慧媛[1];陈彻[1]

第一作者：刘玉

机构：[1]甘肃中医学院医学技术学院,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2014

卷号：34

期号：8

起止页码：705

中文期刊名：肿瘤

外文期刊名：Tumor

收录：CSTPCD;;Scopus;北大核心:【北大核心2011】；CSCD:【CSCD2013_2014】；

基金：2012年度甘肃省高等学校研究生导师科研项目(编号:1206-04)

语种：中文

中文关键词：肝肿瘤;细胞增殖;细胞凋亡;三氧化二砷;AZT;细胞;HepG2

外文关键词：Liver neoplasms; Cell proliferation; Apoptosis; Arsenic trioxide; AZT; Cell, HepG2

摘要：目的 :探讨小剂量三氧化二砷(arsenic trioxide,As2O3)联合3’-叠氮-3’-脱氧胸腺嘧啶核苷(3’-azido-3’-deoxythymidine,AZT)对肝癌HepG2细胞增殖和凋亡的作用及其可能的作用机制。方法 :应用MTT法检测不同浓度As2O3、AZT和As2O3联合AZT对人HepG2细胞的增殖抑制作用并计算联合指数,FCM法检测As2O3、AZT和As2O3联合AZT干预后HepG2细胞的凋亡率,RT-PCR法和蛋白质印迹法检测As2O3、AZT和As2O3联合AZT干预后HepG2细胞中caspase-3、Bcl-2和Bax mRNA及蛋白的表达水平。结果 :As2O3联合AZT干预后,HepG2细胞的增殖抑制率高于各单药组(P<0.05),As2O3联合AZT的联合指数<1,表现出明显的协同效应。As2O3联合AZT干预组HepG2细胞的凋亡率明显高于对照组(未进行药物干预)和各单药组(P<0.05)。As2O3联合AZT干预组HepG2细胞中caspase-3和Bax mRNA及蛋白的表达水平明显高于对照组和各单药组(P<0.05),As2O3联合AZT干预组HepG2细胞中Bcl-2 mRNA和蛋白的表达水平明显低于对照组(P<0.05),As2O3联合AZT干预组HepG2细胞中Bax mRNA和蛋白表达水平与Bcl-2 mRNA和蛋白表达水平间的比值高于对照组(P<0.05)。结论 :As2O3联合AZT可协同抑制HepG2细胞的增殖,这一作用可能与诱导细胞凋亡、上调caspase-3和Bax表达以及下调Bcl-2表达有关。
Objective： To investigate the effects of a small dose of arsenic trioxide （As2O3） combined with 3＇-azido-3＇-deoxythymidine （AZT） on proliferative inhibition and apoptosis of hepatoma HepG2 cells and their possible mechanism. Methods： The proliferation inhibition rates of HepG2 cells after treatment with different concentrations of As2O3 and AZT alone and their combination were detected by MTT assay. The combined index of As2O3 and AZT was calculated. The apoptotic rates of HepG2 cells after treatment with As2O3 and AZT alone and their combination were detected by flow cytometry （FCM）, and the expression levels of caspase-3, Bcl-2 and Bax mRNAs and proteins were analyzed through RT-PCR and Western blotting, respectively. Results： The proliferation inhibition rate of HepG2 cells in combination of As2O3 and AZT group was higher than that in As2O3 and AZT alone groups （both P 〈 0.05）. The value of combined index was less than 1, indicating obvious synergistic effect between As2O3 and AZT. The apoptotic rate of HepG2 cells after treatment with the combination of As2O3 and AZT was higher than those of the control cells （without any treatment） and As2O3 and AZT alone groups （all P 〈 0.05）. The expression levels of caspase-3 and Bax mRNAs and proteins in combination of As2O3 and AZT group were higher than those of the control group （without any treatment） and As2O3 and AZT alone groups （all P 〈 0.05）. The expression levels of Bcl-2 mRNA and protein in combination of As2O3 and AZT group were lower than those of As2O3 and AZT alone groups （both P 〈 0.05）. The ratios of Bax/Bcl-2 mRNA and protein in combination of As2O3 and AZT group were higher than those of the control group （P 〈 0.05）. Condusion： As2O3 in combination with AZT has a synergistic effect on proliferative inhibition of HepG2 cells. This effect may be associated with induction ofapoptosis, up-regulation of caspase-3 and Bax expressions, and down-regulation of Bcl-2 expression.